Causal Mediation Analysis for Difference-in-Difference Design and Panel Data

Advantages of panel data, i.e., difference in difference (DID) design data, are a large sample size and easy availability. Therefore, panel data are widely used in epidemiology and in all social science fields. The literatures on causal inferences of panel data setting or DID design are growing, but no theory or mediation analysis method has been proposed for such settings. In this study, we propose a methodology for conducting causal mediation analysis in DID design and panel data setting. We provide formal counterfactual definitions for controlled direct effect and natural direct and indirect effect in panel data setting and DID design, including the identification and required assumptions. We also demonstrate that, under the assumptions of linearity and additivity, controlled direct effects can be estimated by contrasting marginal and conditional DID estimators whereas natural indirect effects can be estimated by calculating the product of the exposure-mediator DID estimator and the mediator-outcome DID estimator. A panel regression-based approach is also proposed. The proposed method is then used to investigate mechanisms of the effects of the Covid 19 pandemic on the mental health status of the population. The results revealed that mobility restrictions mediated approximately 45 % of the causal effect of Covid 19 on mental health status

An Analysis of Mechanical Constraints when Using Superconducting Gravimeters for Far-Field Pre-Seismic Anomaly Detection

Pre-seismic gravity anomalies from records obtained at a 1 Hz sampling rate from superconducting gravimeters (SG) around East Asia are analyzed. A comparison of gravity anomalies to the source parameters of associated earthquakes shows that the detection of pre-seismic gravity anomalies is constrained by several mechanical conditions of the seismic fault plane. The constraints of the far-field pre-seismic gravity amplitude perturbation were examined and the critical spatial relationship between the SG station and the epicenter precursory signal for detection was determined. The results show that: (1) the pre-seismic amplitude perturbation of gravity is inversely proportional to distance; (2) the transfer path from the epicenter to the SG station that crosses a tectonic boundary has a relatively low pre-seismic gravity anomaly amplitude; (3) the pre-seismic gravity perturbation amplitude is also affected by the attitude between the location of an SG station and the strike of the ruptured fault plane. The removal of typhoon effects and the selection of SG stations within a certain intersection angle to the strike of the fault plane are essential for obtaining reliable pre-seismic gravity anomaly results

The incidence of symptomatic venous thromboembolism following hip fractures with or without surgery in Taiwan

AbstractBackgroundInformation on the incidence of venous thromboembolism (VTE) following hip fractures in Asia is rare. This study will investigate the epidemiology of symptomatic VTE in Taiwanese patients experiencing hip fractures.Methods and resultsWe used Taiwan's National Health Insurance Research Database to retrospectively identify patients (≧45years) who experienced hip fractures from 1998 to 2007 and were followed up for 3months after the discharge. Logistic regression analysis determined the independent risk factors of symptomatic VTE after the fractures. We identified 134,034 patients (mean age: 76.2±9.7years; female: 57.8%) who experienced hip fractures, 83.2% of whom underwent hip surgery. The overall pharmacological thromboprophylaxis rate was 2.7%. The mean length of stay was 11.3±7.9days. The 3-month cumulative incidence of symptomatic VTE was 77 events per 10,000 persons. Multivariate analysis showed that previous DVT, previous PE, varicose veins, cancer, heart failure, renal insufficiency, and older age were independent risk factors of developing VTE.ConclusionsThe incidence of symptomatic VTE after hip fractures is low in Taiwan. Patients rarely received pharmacological thromboprophylaxis following hip fractures. Universal thromboprophylaxis for patients experiencing hip fractures was not necessary in Taiwan, but it should be considered in high-risk populations

Oral Rg1 supplementation strengthens antioxidant defense system against exercise-induced oxidative stress in rat skeletal muscles

BACKGROUND: Previous studies reported divergent results on nutraceutical actions and free radical scavenging capability of ginseng extracts. Variations in ginsenoside profile of ginseng due to different soil and cultivating season may contribute to the inconsistency. To circumvent this drawback, we assessed the effect of major ginsenoside-Rg1 (Rg1) on skeletal muscle antioxidant defense system against exhaustive exercise-induced oxidative stress. METHODS: Forty weight-matched rats were evenly divided into control (N = 20) and Rg1 (N = 20) groups. Rg1 was orally administered at the dose of 0.1 mg/kg bodyweight per day for 10-week. After this long-term Rg1 administration, ten rats from each group performed an exhaustive swimming, and remaining rats considered as non-exercise control. Tibialis anterior (TA) muscles were surgically collected immediately after exercise along with non-exercise rats. RESULTS: Exhaustive exercise significantly (p<0.05) increased the lipid peroxidation of control group, as evidenced by elevated malondialdehyde (MDA) levels. The increased oxidative stress after exercise was also confirmed by decreased reduced glutathione to oxidized glutathione ratio (GSH/GSSG ratio) in control rats. However, these changes were completely eliminated in Rg1 group. Catalase (CAT) and glutathione peroxidase (GPx) activities were significantly (p<0.05) increased by Rg1 in non-exercise rats, while no significant change after exercise. Nevertheless, glutathione reductase (GR) and glutathione S-transferase (GST) activities were significantly increased after exercise in Rg1 group. CONCLUSIONS: This study provide compelling evidences that Rg1 supplementation can strengthen antioxidant defense system in skeletal muscle and completely attenuate the membrane lipid peroxidation induced by exhaustive exercise. Our findings suggest that Rg1 can use as a nutraceutical supplement to buffer the exhaustive exercise-induced oxidative stress

SirT1—A Sensor for Monitoring Self-Renewal and Aging Process in Retinal Stem Cells

Retinal stem cells bear potency of proliferation, self-renewal, and differentiation into many retinal cells. Utilizing appropriate sensors one can effectively detect the self-renewal and aging process abilities. Silencing information regulator (SirT1), a member of the sirtuin family, is a NAD-dependent histone deacetylase and an essential mediator for longevity in normal cells by calorie restriction. We firstly investigate the SirT1 mRNA expression in retinal stem cells from rats and 19 human eyes of different ages. Results revealed that SirT1 expression was significantly decreased in in vivo aged eyes, associated with poor self-renewal abilities. Additionally, SirT1 mRNA levels were dose-dependently increased in resveratrol- treated retinal stem cells. The expression of SirT1 on oxidative stress-induced damage was significantly decreased, negatively correlated with the level of intracellular reactive oxygen species production. Treatment with resveratrol could effectively further reduce oxidative stress induced by H2O2 treatment in retinal stem cells. Importantly, the anti-oxidant effects of resveratrol in H2O2-treated retinal stem cells were significantly abolished by knockdown of SirT1 expression (sh-SirT1). SirT1 expression provides a feasible sensor in assessing self-renewal and aging process in retinal stem cells. Resveratrol can prevent reactive oxygen species-induced damages via increased retinal SirT1 expression

Persistently Elevated HBV Viral-Host Junction DNA in Urine as a Biomarker for Hepatocellular Carcinoma Minimum Residual Disease and Recurrence: A Pilot Study

Hepatitis B virus (HBV)-host junction sequences (HBV-JSs) has been detected in the urine of patients with HBV infection. This study evaluated HBV-JSs as a marker of minimum residual disease (MRD) and tumor recurrence after treatment in HBV-hepatocellular carcinoma (HCC) patients. Archived serial urine DNA from two HBV–HCC with recurrence as confirmed by MRI and four HBV-related cirrhosis (LC) patients were used. Urinary HBV-JSs were identified by an HBV-targeted NGS assay. Quantitative junction-specific PCR assays were developed to investigate dynamic changes of the most abundant urinary HBV-JS. Abundant urinary HBV-JSs were identified in two cases of tumor recurrence. In case 1, a 78-year-old female with HBV- HCC underwent a follow-up MRI following microwave ablation. While MRI results were variable, the unique HBV-JS DNA, HBV-Chr17, steadily increased from initial diagnosis to HCC recurrence. In case 2, a 74-year-old male with HBV–HCC contained two HBV-JS DNA, HBV-Chr11 and HBV-TERT, that steadily increased after initial HCC diagnosis till recurrence. One LC examined had HBV-TERT DNA detected, but transiently in 3.5 years during HCC surveillance. HBV-JS DNA was persistently elevated prior to the diagnosis of recurrent HCC, suggesting the potential of urinary HBV-JS DNA to detect MRD and HCC recurrence after treatment

Molecular Characterization of Tb, a New Approach for an Ancient Brucellaphage

Tb (Tbilisi), the reference Brucellaphage strain, was classified as a member of the Podoviridae family with icosahedral capsids (57 ± 2 nm diameter) and short tails (32 ± 3 nm long). Brucellaphage DNA was double stranded and unmethylated; its molecular size was 34.5 kilobase pairs. Some sequences were found through RAPD analysis, TA cloning technology, and structural proteins were observed by using SDS-PAGE. Thus, the results have laid the foundation for the wider use of Brucellaphage’s basic mechanisms and practical applications

Stem Cell-Based Neuroprotective and Neurorestorative Strategies

Stem cells, a special subset of cells derived from embryo or adult tissues, are known to present the characteristics of self-renewal, multiple lineages of differentiation, high plastic capability, and long-term maintenance. Recent reports have further suggested that neural stem cells (NSCs) derived from the adult hippocampal and subventricular regions possess the utilizing potential to develop the transplantation strategies and to screen the candidate agents for neurogenesis, neuroprotection, and neuroplasticity in neurodegenerative diseases. In this article, we review the roles of NSCs and other stem cells in neuroprotective and neurorestorative therapies for neurological and psychiatric diseases. We show the evidences that NSCs play the key roles involved in the pathogenesis of several neurodegenerative disorders, including depression, stroke and Parkinson’s disease. Moreover, the potential and possible utilities of induced pluripotent stem cells (iPS), reprogramming from adult fibroblasts with ectopic expression of four embryonic genes, are also reviewed and further discussed. An understanding of the biophysiology of stem cells could help us elucidate the pathogenicity and develop new treatments for neurodegenerative disorders. In contrast to cell transplantation therapies, the application of stem cells can further provide a platform for drug discovery and small molecular testing, including Chinese herbal medicines. In addition, the high-throughput stem cell-based systems can be used to elucidate the mechanisms of neuroprotective candidates in translation medical research for neurodegenerative diseases

A Randomised Placebo-Controlled Trial of a Traditional Chinese Herbal Formula in the Treatment of Primary Dysmenorrhoea

BACKGROUND: Most traditional Chinese herbal formulas consist of at least four herbs. Four-Agents-Decoction (Si Wu Tang) is a documented eight hundred year old formula containing four herbs and has been widely used to relieve menstrual discomfort in Taiwan. However, no specific effect had been systematically evaluated. We applied Western methodology to assess its effectiveness and safety for primary dysmenorrhoea and to evaluate the compliance and feasibility for a future trial. METHODOLOGY/PRINCIPAL FINDINGS: A randomised, double-blind, placebo-controlled, pilot clinical trial was conducted in an ad hoc clinic setting at a teaching hospital in Taipei, Taiwan. Seventy-eight primary dysmenorrheic young women were enrolled after 326 women with self-reported menstrual discomfort in the Taipei metropolitan area of Taiwan were screened by a questionnaire and subsequently diagnosed by two gynaecologists concurrently with pelvic ultrasonography. A dosage of 15 odorless capsules daily for five days starting from the onset of bleeding or pain was administered. Participants were followed with two to four cycles for an initial washout interval, one to two baseline cycles, three to four treatment cycles, and three follow-up cycles. Study outcome was pain intensity measured by using unmarked horizontal visual analog pain scale in an online daily diary submitted directly by the participants for 5 days starting from the onset of bleeding or pain of each menstrual cycle. Overall-pain was the average pain intensity among days in pain and peak-pain was the maximal single-day pain intensity. At the end of treatment, both the overall-pain and peak-pain decreased in the Four-Agents-Decoction (Si Wu Tang) group and increased in the placebo group; however, the differences between the two groups were not statistically significant. The trends persisted to follow-up phase. Statistically significant differences in both peak-pain and overall-pain appeared in the first follow-up cycle, at which the reduced peak-pain in the Four-Agents-Decoction (Si Wu Tang) group did not differ significantly by treatment length. However, the reduced peak-pain did differ profoundly among women treated for four menstrual cycles (2.69 (2.06) cm, mean (standard deviation), for the 20 women with Four-Agents-Decoction and 4.68 (3.16) for the 22 women with placebo, p = .020.) There was no difference in adverse symptoms between the Four-Agents-Decoction (Si Wu Tang) and placebo groups. CONCLUSION/SIGNIFICANCE: Four-Agents-Decoction (Si Wu Tang) therapy in this pilot post-market clinical trial, while meeting the standards of conventional medicine, showed no statistically significant difference in reducing menstrual pain intensity of primary dysmenorrhoea at the end of treatment. Its use, with our dosage regimen and treatment length, was not associated with adverse reactions. The finding of statistically significant pain-reducing effect in the first follow-up cycle was unexpected and warrants further study. A larger similar trial among primary dysmenorrheic young women with longer treatment phase and multiple batched study products can determine the definitive efficacy of this historically documented formula. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN23374750